Barringtonia comprise the largest genus of plants within the family Lecythidaceae and are widely distributed in the tropical regions of Asia, Malaysia and the Pacific. [1]
Barringtonia are trees or shrubs ranging in size from 2 m to in excess of 25 m. Four species are known to occur in Northern Australia [2], three of which, B. racemosa [(L.) Spreng], B. calyptrate [(Mietrs) R. Br. ex Bailey] and B. asiatica [(L.) Kurtz] are known only from north Queensland. The fourth Australian species, B. acutangula [(L.) Gaertn], has wider distribution, being found across Northern Australia from North Queensland to North Western Australia. Barringtonia acutangula has been further divided into two subspecies, B. acutangula ssp. acutangula and B. acutangula ssp. spicata [1]. The latter of these is found throughout the Barringtonia distribution area whereas the former is restricted to Northern Australia.
Throughout their range many Barringtonia species have been used in variety of ways by local people. One common use of Barringtonia species is as a fish poison [2-5]. Several species have been reported as fish poisons including B. acutangula [2-4, 6-11], B. speciosa [5], B. racemosa [2, 3, 10-12], B. asiatrica [2, 3, 5, 10, 11] and B. calyptrate [10]. Although the fruit and bark of the tree is often used as a fish poison [2, 3, 5-12], several other plant organs, including leaves [8, 11], roots [4, 8, 9, 11], seeds [2, 9, 10, 12] and wood [12], have also been used. The leaves, fruit and seeds of several species are known to be edible [3, 9, 12-15].
Several other properties and uses of Barringtonia species have been reported. These include the use of B. racemosa as a tanning agent, due to the presence of tannins, [3, 12, 16] and as an insecticide reportedly to be approximately half as potent as nicotine [12,16, 17]. The fruit of Barringtonia has been used to poison wild pig [12]. In addition the seed of B. racemosa and the fruit of B. asiatica has been used for suicide and administration with “. . . homicidal intent . . . ” [11, 12], coconut milk being an antidote. These toxic properties may be due to the presence of HCN which has been demonstrated in high concentrations in the kernel of B. asiatica [11].
Many of the Barringtonia species have found extensive use as traditional medicines and the fruit of B. acutangula has been called “Nurse fruit” [6]. All parts of the plant have been used and applications have been both internal and external. Preparation of applications may involve drying and powdering, extraction with hot or cold water, heating or juicing [3, 11, 12, 16, 18]. External applications tend to focus, as expected, on skin disease. Ailments such as general wounds, rheumatism, eczema, ulcers, scabies, tinea, ringworm, itches, inflammation and even leprosy have been treated with Barringtonia species [3, 11, 12, 16, 18]. Seeds in powered form have been used as a snuff to relieve headache whereas heated seeds are aromatic and have been used to assist in colic and parturition [3]. External applications to assist ophthalmia, chest cold and pain, asthma, fever, colic, flatulence, non-venereal stricture, sore throat and stomach ache have also been reported [3, 6, 11, 12, 16, 18].
Common internal used of Barringtonia are for the relief of diarrhoea, dysentery and stomach ache, as an emetic, expectorate and laxative [3, 6, 8-12, 16, 18, 19]. Preparations of some species are taken as a bitter tonic [3, 8, 9, 11, 18, 19] and the seed of B. racemosa is taken as a vermifuge [18].
As fish poisons, Barringtonia species, in particular B. actungula [4], were used extensively in Australia, however it seems that little use was made of Barringtonia species as medicines compared with other regions in which the plants are located. In Australian, Barringtonia extracts have been used for skin complaints such as wounds, boils and chickenpox (B. racemosa and B. acutangula), for chest pain and fever (B. calyprata), in ophthalmia, colic, parturition and to induce vomiting (B. acutangula) [10, 11, 16, 18]. More detailed accounts of the uses of Barringtonia sp. can be found in the literature (eg [3, 12, 18]).
In view of the wide traditional application of Barringtonia species as medicinal plants, it is surprising that the chemical nature of the bioactive constituents has attracted little attention.
The presence of saponin-like glycosides in B. insingnis, B. vriesei and B. racemosa was demonstrated as early as 1898 (reported in [6]). Subsequently, in 1901, a saponin was isolated from B. speciosa which yielded, on hydrolysis, glucose and barringtogenin (reported in [20], although [6] reports the species as B. spinosa). The same author also reported the presence of a second sapogenin, namely barringtogenitin. Nozoe isolated A1-barrinin and A1-barrigenin from the seeds of B. asiatica and subsequently reported that the saponin of A1-barrinin contained gluconic acid, d-glucose, d-galactose and a methyl pentose [21, 22]. Alkaline hydrolysis of A1-barrigenin gave tiglic acid and a new aglycone, A1-barrigenol [23]. Acetylation of A1-barrigenin also led to the isolation of a second aglycone, A2-barrigenol [23].
The presence of high concentrations of saponins was reported from the seeds, leaves and bark of B. acutangula and B. racemosa and three sapogenins were identified [20]. Much of the ensuing work aimed to isolate and characterise the nature of these saponins.
The structure of A1-barrigenol as first assigned by Cole et al. in 1955 is shown in FIG. 1.
During the 1950's, there was a growing interest in saponins and sapogenins as evidenced by the number of publications in which, using mainly degradative techniques, structures were assigned and revised. The first sapogenins isolated from a Barringtonia species after A1- and A2-barrigenol were barringtogenol and barringtogenic acid which were isolated from the fruit of B. racemosa [25] and which structures are shown in FIG. 2.
Barringtonia acutangula continued to be a source of novel saponins and sapogenins. Again from the fruit of this species, a series of compounds, barringtogenol B, C, D, and E, were isolated and their structures explored [8, 26-34].
Barringtogenol C was isolated from B. acutangula fruits and the structure assigned by chemical techniques as previously described (FIG. 4) (eg [8, 26, 27, 31-34]).
Barringtogenol D, again isolated from B. acutangula fruit, was described by Barua et al [26] and a structure proposed by Chakraborti and Barua [29,30] (FIG. 5).
Barringtogenol E was isolated from the branch wood of B. acutangula and a structure was assigned using mass spectral and chemical information (FIG. 6) [8, 28]. It was noted that barringtogenol E was perhaps the first example of a triterpene benzoate isolated from nature [8, 28].
Other compounds isolated from B. acutangula include tanginol [8, 35, 36] as shown in FIG. 7 and barrinic acid shown in FIG. 8 [37].
Several compounds have been isolated, again from B. acutangula, and their structures assigned in part using NMR. These include barrigenic acid, the 19β-isomer of barrinic acid (fruit) [36] and acutangulic and tangulic acids (leaves) (FIG. 9) [3840].
It was not until 1991 [41] that the structure of an intact saponin from B. acutangula was published. Spectral and chemical data led to the structure being assigned as 2α,3β,19α-trihydroxy-olean-12-ene-dioic acid 28-O-β-D-glucopyranoside (FIG. 10) [41].
Shortly after the publication of this structure the same group published the complete structures of three more saponins from the seeds of B. acutangula, barringtosides A, B and C (FIG. 11) [42].
Although this Barringtonia species has been used as medicinal plants for a wide variety of ailments, no information concerning the biological activity of any of the isolated triterpenes can be located. However, it is known that triterpenes have some anti-inflammatory activity (eg [43, 44]). The astringent properties of the bark of Barringtonia have been attributed to the presence of tannins [16, 18] which are also known to possess anti-microbial properties (eg [45]). The general use of Barringtonia species as preparation for skin sores, wounds and other skin complaints may be due to the presence of these tannins. Many of the reported effects induced by preparations from these trees can be accounted for by the activity of steroids (eg anti-inflammatory, anti-asthmatic, anti-rheumatic etc) and the presence of the β- and (-sitosterol and stigmasterol-3β-O-D-glucoside in extracts from Barringtonia species may explain some of these activities. It is also well known that saponins exhibit a wide range of biological activities, many of which could explain the observed medicinal properties outlined earlier (eg [46, 47]).
As is evident from the preceding discussion, the dominant group of compounds found in Barringtonia thus far studies are saponins. Saponins are an important class of secondary metabolites that are widespread in plants and lower marine organisms. It has been reported that approximately 79% of all plants surveyed contain saponins [48]. It has also been proposed that saponins are produced as defensive agents by the plant [48]. Increasing numbers of saponins are being isolated from lower marine organisms, but so far have been isolated from the phylum Echinodermata, in particular sea cucumbers (Holothuroidea) and starfish (Asteroidea) [46].
Saponins consist of three main components, an aglycone (genin or sapogenin), such as a triterpene, a steroid or a steroidal alkaloid, one or more sugar chains, commonly D-glucose, D-galactose, D-glucuronic acid, D-galacturonic acid, L-rhamnose, L-arabinose, D-xylose and D-fucose and sometimes acids, such as angelic and tiglic acids [46,47, 49]. Saponins are further classified as mono-, bi- or tri-desmosides according to the number of sugar chains which are attached to the aglycone [47].
The haemolytic, molluscidal and piscicidal activities of saponins are well characterised and have even been used as assay techniques in bio-guided fractionations of plant and animal extracts (eg [47, 48, 50, 51]). However haemolytic activity varies greatly or may be absent altogether and molluscicidal activity is somewhat dependent on the structure of the saponin [46, 47]. As expected there are many publications on the biological and pharmacological properties of saponins, examples of which can be seen in [46, 47].
Analgesic activity has been demonstrated in a small number of saponins. The following is an example of some of the saponins found to have analgesic effects. Using the acetic acid writhing test it was shown that barbatoside A (ED50 95 mg/kg) and B (ED50 50 mg/kg), glycosides of quaillic acid from Dianthus barbatus, were more active than acetylsalic acid (ED50 125 mg/kg) [52]. An intraperitoneal (ip) injection of a saponin preparation from Dolichos falcatus at 5 mg/kg was shown to produce marked analgesic effect to pain induced by exposure of 55° C. in mice [53]. An extract of Platycodon grandiflorum also induced analgesia in mice when injected subcutaneous (sc) at a dose of 2 g/kg [54]. One of the active ingredients is stated as being platicodin and the dose received by the mice was equivalent to 160 mg/kg. The effects were comparable to 100-200 mg/kg aspirin. Injection (ip, 100-250 mg/kg) of the total saponin preparation from Panax notoginseng was found to act faster but for shorter durations than morphine and I-tetrahydropalmatine and was comparable to aminopyrine (150 mg/kg) [55]. It was also noted that the saponin preparation induced a sedative effect, decreased the ED50 of pentobarbital in sleep induction, prolonged thiopental induced sleep and showed synergistic effects with chlorpromazine in CNS inhibition [55]. A number of dianosides were isolated and characterised from Dianthus superbus ver. Iongicalycinus [56-58]. Dianosides A and B were found to significantly inhibit acetic acid induced writhing at 10 and 30 mg/kg (sc) with dianoside B the more potent [56]. In a detailed examination of the pharmacological effects of glycosidal fraction obtained from Maesa chisa var. augustifolia, Gomes et al [59] demonstrated, among other things, analgesia in the writhing test in mice. A 33% inhibition was observed in p-phenylquinonone induced writhing in contrast to a 52% inhibition observed in acetic acid induced writhing. By comparison, aspirin inhibited p-phenylquinone induced writhing by 85% and acetic acid induced writhing by 80%. The absence of straubtail phenomena and lack of activity in both the hot plate and the tail flick tests suggests that the analgesia produced by the glycoside fraction was different to that produced by narcotics.